April 16, 2006
Human Stem Cells Partially Fix Rodent Stroke Disability

Researchers at the Medical College of Georgia have demonstrated the ability of a commercial human stem cell line to partially repair surgically induced stroke-like damage in rat brains.

A single dose of adult donor stem cells given to animals that have neurological damage similar to that experienced by adults with a stroke or newborns with cerebral palsy can significantly enhance recovery from these types of injuries, researchers say.

Using a commonly utilized animal model for stroke, researchers administered a dose of 200,000-400,000 human stem cells into the brain of animals that had experienced significant loss of mobility and other functions. The stem cells used in the study were a recently discovered stem cell type, referred to as multipotent adult progenitor cells, or MAPCs.

Treated animals experienced at least 25 percent greater improvement in motor and neurological performance than controls, said Dr. Cesario V. Borlongan, neuroscientist at the Medical College of Georgia and the Veterans Affairs Medical Center in Augusta.

Improvement in function continued for the length of the study. This suggests that even greater improvement would have been seen over additional months. Also, it opens up the possibility that additional treatment doses might yield even greater improvement.

Following the stroke, both control animals and those that received a single injection of stem cells were evaluated for a period of up to 2 months. Improvements in stem cell treated animals included enhanced performance across the range of tests, which examined strength, balance, agility and fine motor skills, and also included greater recovery of injured tissue.

“A single dose of the cells produce robust behavioral recovery at an early period post-transplantation and the recovery was durable, lasting up to two months, which was the entire length of this study,” Dr. Borlongan said. “Furthermore, animals continued to show improvement over time.” In the newborn model of ischemic injury, enhanced recovery was found within two weeks.

Even though less than 1 percent of the transplanted cells were present two months later, animals receiving treatment developed new neurons, apparently formed from endogenous stem cells. “The mechanism that we are putting forward is these donor cells are secreting nourishing trophic factors that are helping the host brain cells survive and stimulating stem cells from the host to multiply,” Dr. Borlongan said.

I can imagine such a treatment providing benefit even to those who do not suffer from stroke or cerebral palsy. Aged brains with slowly dividing stem cells could get partially rejuvenated if injected stem cells could stimulate existing cells to divide.

This method of treatment for stroke does not repair the core location of damage. However, repair on the periphery could prevent the core damage area from getting even larger and could make the difference between, for example, being wheelchair bound or walking with a cane. Or it could mean the difference between drooling out the side of one's mouth or being able to keep one's mouth closed.

In the adult stroke model, MCG researchers found giving stem cells increased the number of injured cells that survived in the area just outside the area of greatest damage, also referred to as the ischemic core, by 5-20 percent.

“Up to this point, all the treatment approaches, including transplantation and tPA, cannot get rid of that ischemic core,” Dr. Borlongan said. “But outside of that core there is a lining, what we call the penumbra, and that penumbra, if you do not treat it over time, becomes part of the core. We are showing, that even one week after a stroke, we are able to increase the number of cells surviving along that penumbra and that is how we feel it is producing significant recovery, by rescuing cells within the penumbra.”

What we most need are stem cell therapies, gene therapies, and still other therapies that will go into the vascular system and repair blood vessels that put us at risk of stroke. Any therapy aimed at restoring function after a stroke won't be able to put back neurons that held memories or that were trained to do complex physical movements such as, say, playing a musical instrument. Better not to lose the neurons in the first place.

The stem cells used in this experiment came from a Cleveland Ohio biotech company named Athersys.

Athersys, Inc., a Cleveland-based biopharmaceutical company pursuing cell therapy programs in cardiovascular disease, stroke, cancer and other diseases, funded the research in which previously frozen human or rodent multipotent adult progenitor cells,  which the company calls MultiStem™, were thawed and injected directly into the brain.

Researchers believe that MultiStem™ cells are able to deliver a therapeutic benefit in multiple ways, for example by producing factors that limit tissue damage and stimulate repair, according to Dr. Gil Van Bokkelen, the company’s chairman and chief executive officer. In addition, MultiStem™ cells can safely mature into a broad range of cell types and can be produced on a large scale, something which should ease the move toward clinical studies and eventual clinical use. “Given the number of stroke victims each year, it would be a big step forward if a safe and effective stem cell therapy could be produced, conveniently stored, and efficiently delivered on a widespread basis. We believe that we can achieve that with MultiStem™,” commented Dr. Van Bokkelen.

As stem cell therapies become used to treat a wider range of diseases and disorders the revenue from sales will feed back toward the development of improvements and the development of stem cell therapies for yet more conditions and problems. We are on the threshold of a virtuous cycle of stem cell development funded by the enormous amounts of money in the medical industry. Sales of stem cell therapies will replace far less effective therapies and also shift money away from nursing homes and palliative treatments.

Update: Another study using stem cells to repair neuron damage found that a special gel can align the growth of neural stem cells to help bridge spinal cord injury gaps.

The second study addressed a significant problem in the use of stem cells for spinal cord repair, that of directing cells to align in the proper direction along the cord. Misdirected or undirected cell orientation limits the ability of injured nerves to reconnect with other nerve cells further down the spinal cord. “A regrowth-directing structured scaffold is required for spinal cord repair,” said lead study author Norbert Weidner, MD, of the University of Regensburg, Germany.

The research group tested anisotropic capillary hydrogels (ACH) made of a seaweed derivative, which have an internal structure that preferentially guides axons (nerve cell extensions) in one direction. In brain slice cultures, they showed that ACH promoted regrowth of existing axons and improved their ability to reconnect with their target nerve cells. They then tested this strategy in adult rats with damaged spinal cords, where ACH promoted directional regrowth across the scaffold. Ongoing studies demonstrate that ACH can be "seeded" with neural stem cells, which now align properly and may further enhance the regenerative capacity of ACH.

To give you some measure of the potential benefit of a treatment that could repair damaged spinal cords in the United States about a quarter million people have spinal cord injuries and the average age at the time of injury is about 28 years old. So a lot of people will gain decades of greater mobility and richer lives when their spinal cord injuries become repairable. The economic value of effective spinal cord repair techniques will be enormous.

Share |      Randall Parker, 2006 April 16 04:23 PM  Biotech Stem Cells

diana said at April 16, 2006 4:28 PM:

What I'm waiting for is the day they can grow human teeth & implant them in your jaw. Now that will be a day for rejoicing. Hallelujah!

remo willams said at April 16, 2006 7:39 PM:

From what I've read, regenerated teeth should be available within a few years.

Brett Bellmore said at April 17, 2006 5:35 PM:

I sometimes in my darker moments suspect that the singularity will consist of lab rats taking over the universe, due to regulation delaying human trials of all the various treatments and augmentations.

diana said at April 17, 2006 6:24 PM:

Remo: I read that a few years ago. Dentistry isn't a priority.

remo willams said at April 19, 2006 4:16 AM:

I agree! We need to get serious about the true scorge ....Funnel all funds to quicken hair cloning! (around 2010)

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